Androgen level variations, clinical response to LHRH agonists and changes in the quality of life subscales in metastatic prostate cancer--speculations about possible role of the monoamine system.
The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result of the change in the level of monoamines in CNS under Zoladex.
Popov
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I
Institute of Oncology and Radiology of Serbia, Belgrade, Yugoslavia.
Jelić
S
S
Radosavljević
D
D
Nikolić-Tomasević
Z
Z
D000135:Acid Phosphatase / Q000097:blood; D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015114:Androstenediol / Q000097:blood; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001859:Bone Neoplasms / Q000556:secondary; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011788:Quality of Life; D013739:Testosterone / Q000097:blood*
D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D015114:Androstenediol; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase